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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0100v1 198/2/403    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stolte, E. Articles by Flik, G. Search for Related Content PubMed PubMed Citation Articles by Stolte, E. Articles by Flik, G.

E Stolte, Cell Biology and Immunology, WUR, Wageningen, Netherlands
A De Mazon, Cell Biology and Immunology, WUR, Wageningen, Netherlands
K Leon, Wageningen, Netherlands
M Jesiak, Wageningen, Netherlands
N Bury, Kings College London, London, United Kingdom
A Sturm, Stirling University, Stirling, United Kingdom
H Savelkoul, Wageningen, Netherlands
L van Kemenade, Cell Biology and Immunology, WUR, Wageningen, Netherlands
G Flik, Department of Animal Physiology, University of Nijmegen, Nijmegen, 'NL-6525 ED , Netherlands

Correspondence: Gert Flik, Email: g.flik{at}science.ru.nl

Abstract

In higher vertebrates, mineralo- (aldosterone) and glucocorticoids (cortisol/corticosterone) exert their multiple actions via specific transcription factors, glucocorticoid (GR) and mineralocorticoid (MR) receptors. Teleostean fishes lack aldosterone and mineral regulatory processes seem under dominant control by cortisol. Despite the absence of the classical mineralocorticoid aldosterone, teleostean fishes do have a mineralocorticoid receptor (MR) with cortisol and possibly 11-deoxycorticosterone (as alternative for aldosterone) as predominant ligands. We studied corticoid receptors in common carp (Cyprinus carpio L.). Through homology cloning and bio-informatic analysis we found duplicated GR genes and a single MR gene. The GR genes likely result from a major genomic duplication event in the teleostean lineage; we propose that the gene for a second MR was lost. Transactivation studies show that the carp GRs and MR have comparable affinity for cortisol; the MR has significantly higher sensitivity to 11-deoxycorticosterone, and this favors a role for DOC as MR ligand in fish physiology. Messenger RNA of the GRs and the MR is expressed in forebrain (in pallial areas homologous to mammalian hippocampus), in CRH-cells in the preoptic nucleus (NPO) and in the pituitary pars distalis ACTH-cells, three key neural/endocrine components of the stress axis. After exposure to prolonged and strong (not to mild acute) stressors, mRNA levels of both GRs and MR become down-regulated in the brain, but not in the NPO CRH-cells or pituitary ACTH-cells. Our data predict a function in stress physiology for all CRs and suggest telencephalon as a first line cortisol target in stress.

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